Detecting radio- and chemoresistant cells in 3D cancer co-cultures using chromatin biomarkers.

ABSTRACT: The heterogenous treatment response of tumor cells limits the effectiveness of cancer therapy. While this heterogeneity has been linked to cell-to-cell variability within the complex tumor microenvironment, a quantitative biomarker that identifies and characterizes treatment-resistant cell populations is still missing. Herein, we use chromatin organization as a cost-efficient readout of the cells' states to identify subpopulations that exhibit distinct responses to radiotherapy. To this end, we developed a 3D co-culture model of cancer spheroids and patient-derived fibroblasts treated with radiotherapy. Using the model we identified treatment-resistant cells that bypassed DNA damage checkpoints and exhibited an aggressive growth phenotype. Importantly, these cells featured more condensed c

SUBMITTER: Pekec T 

PROVIDER: S-EPMC10673941 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature